Health Utility Measures Among Patients with Androgenetic Alopecia After Hair Transplant.

BACKGROUND: Hair loss causes significant psychosocial distress to patients. Health utility measurements offer an objective, quantitative assessment of health-related quality of life (QOL). METHODS: We performed a prospective cohort study on patients with hair loss between January 1, 2018 and December 31, 2020. Patient metrics were compared with layperson perception of alopecia, prospectively collected between August 1 and December 31, 2017. Health utility measures were quantified using the visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO) in quality-adjusted life-years (QALYs) and relative to the minimal clinically important difference (MCID). Bonferroni correction to the significance threshold was performed. RESULTS: Thirty-one patients with alopecia were compared with 237 laypeople. Patient metrics for female hair loss were all significantly lower than laypeople measures (VAS QALYs 0.65 ± 0.21 vs. 0.83 ± 0.18, p = 0.0001). Mean SG QALYs were lower for patients in the male alopecia state (0.86 ± 0.23 vs. 0.96 ± 0.12, p = 0.0278). Post-hair transplant improvement in TTO was significantly greater for patients (+ 0.08 ± 0.12 vs. + 0.02 ± 0.09, p = 0.0070) and significantly more often exceeded the MCID (45.2% vs. 16.9%, p = 0.0006). CONCLUSIONS: Alopecia negatively impacts QOL, and the true patient experience is more taxing than what is perceived by laypeople. Hair transplantation improves QOL more for male patients than common perception. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Thrombospondin-4 mediates hyperglycemia- and TGF-beta-induced inflammation in breast cancer.

Inflammation drives the growth of tumors and is an important predictor of cancer aggressiveness. CD68, a marker of tumor-associated macrophages (TAM), is routinely used to aid in prognosis and treatment choices for breast cancer patients. We report that thrombospondin-4 (TSP-4) mediates breast cancer inflammation and growth in mouse models in response to hyperglycemia and TGF-beta by increasing TAM infiltration and production of inflammatory signals in tumors. Analysis of breast cancers and noncancerous tissue specimens from hyperglycemic patients revealed that levels of TSP-4 and of macrophage marker CD68 are upregulated in diabetic tissues. TSP-4 was colocalized with macrophages in cancer tissues. Bone-marrow-derived macrophages (BMDM) responded to high glucose and TGF-beta by upregulating TSP-4 production and expression, as well as the expression of inflammatory markers. We report a novel function for TSP-4 in breast cancer: regulation of TAM infiltration and inflammation. The results of our study provide new insights into regulation of cancer growth by hyperglycemia and TGF-beta and suggest TSP-4 as a potential therapeutic target.

Increased pathologic upstaging with rising time to treatment initiation for head and neck cancer: A mechanism for increased mortality.

BACKGROUND: Time to treatment initiation (TTI) is increasing and is associated with worsening survival. In the current study, the authors sought to identify a mechanism for this relationship by assessing the effect of TTI on clinical-to-pathologic upstaging in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Using the National Cancer Data Base, the authors analyzed patients receiving definitive surgery for SCC of the oral cavity, oropharynx, larynx, and hypopharynx from 2005 through 2014. The primary outcome was T, N, or stage group upstaging, defined as higher pathologic stage than clinical stage. TTI was defined as the time between diagnosis and surgery. Multivariable logistic and Cox proportional hazards regression modeled upstaging and survival, respectively. RESULTS: Cohorts of 60,194 patients, 51,380 patients, and 52,980 patients, respectively, with complete T, N, and stage group data were included. N upstaging was most common (18.6%), followed by stage group (17.4%) and T (12.1%) upstaging; all types were predicted by TTI. Compared with a TTI of 1 to 6 days, TTIs as short as 7 to 13 days (odds ratio, 1.20; P = .038) or ≥ 70 days (odds ratio, 2.04; P < .001) were found to predict T upstaging, a finding that is consistent for N and stage group upstaging. Using restricted cubic splines, relative odds of T and stage group upstaging escalated to 2.25 and 1.93, respectively, at a TTI of 365 days. In survival analyses, T (hazard ratio [HR], 1.53), N (HR, 1.88), and stage group (HR, 1.69) upstaging all predicted mortality (P < .001), whereas TTI only predicted mortality after 70 days (HR, 1.11; P = .023). CONCLUSIONS: Tumor progression, measured by clinical-to-pathologic upstaging, increases mortality for patients with HNSCC experiencing treatment delays. Cancer 2018;124:1400-14. © 2018 American Cancer Society.

Surgical management of patients with Eagle syndrome.

OBJECTIVE: Eagle syndrome, a spectrum of disease resulting from an elongated styloid process and/or calcified stylohyoid ligament, lacks standardized recommendations regarding indications for surgical intervention and approach. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary care institution. SUBJECTS: Patients treated surgically for Eagle syndrome between January 2011 and June 2017. METHODS: Patients were diagnosed with Eagle syndrome based on thorough clinical workup and assessment. The primary outcome was improvement in pain severity following surgery, with complete resolution of pain being considered clinically meaningful. Wilcoxon rank-sum tests and Fisher's exact were used to compare numerical and categorical variables, respectively. RESULTS: Twenty-one patients were diagnosed with Eagle syndrome and underwent surgical resection of the styloid process. Patients most often complained of neck pain (81%), throat pain (62%), and ear pain (48%). Among these patients, 57% of procedures featured a transcervical approach, while the remaining 43% were transoral. The vast majority (90%) of patients experienced improvement in pain severity from a median of 6.0 before surgery to 0.0 afterwards (p < 0.01) as 62% experienced complete resolution. Using multivariable linear regression to model changes in pain severity, neck pain (ß = -1.69, p < 0.01) and jaw pain (ß = -0.93, p = 0.03) predicted greater relief, while headache (ß = 0.82, p = 0.04) predicted an inferior response. Adverse events were uncommon and typically resolved within three months, with 24% experiencing first bite syndrome and 19% reporting numbness. CONCLUSIONS: Transcervical and transoral styloidectomy are effective treatments for Eagle syndrome with minimal adverse effects. Patients with classic symptoms of neck or jaw pain benefit most from surgery.

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal.

OBJECTIVE: Spinal cord stimulation (SCS) is a safe, reversible surgical treatment for complex regional pain syndrome and failed back surgery syndrome refractory to conventional medical management. Paddle electrodes are routinely used for the permanent implant because of the reduced risk of migration, lower energy requirements, and expanded coverage options. The risks associated with paddle lead removal are not well defined in the literature. METHODS: We retrospectively reviewed the outcomes of all patients at the Cleveland Clinic who underwent removal of SCS paddle electrodes between 2009 and 2016. RESULTS: We identified 68 patients during this interval who had a paddle electrode removed. The most common reason for removal was loss of coverage or effect (75%), followed by infection (13.24%), and the need for magnetic resonance imaging for diagnostic purposes (8.82%). Postoperative complications occurred in eight patients (11.75%), two of which were classified as major (2.94%). One of these patients developed a postoperative cerebrospinal fluid leak, and another suffered a large suprafascial hematoma. Both patients underwent reoperation. Minor complications were reported in six patients (8.82%) and included wound dehiscence, infection, and prolonged ileus in one case. On average, patients who developed complications lost 20 mL more blood during surgery than those who did not develop complications (p = 0.006). CONCLUSION: One of the benefits of SCS therapy is the reversibility of the procedure. However, removal is not without some risk though the overall risk of minor or major complication is low. Patients who are considering removal should be counseled appropriately. Prophylactic removal is not recommended. However, when removal is needed, surgeons and pain specialists must be familiar with these complications and their management.

The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies.

To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 and 5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a significantly increased rate of RN among lesions treated with upfront SRS and WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p < 0.01). Among these therapies, significantly increased rates of RN were observed with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely delivered concurrently with SRS in the management of newly-diagnosed brain metastases. However, the rate of radiographic RN is significantly increased with the addition of concurrent systemic therapies to SRS and WBRT.

Proangiogenic Properties of Thrombospondin-4.

OBJECTIVE: Thrombospondin-4 (TSP-4) is 1 of the 5 members of the thrombospondin protein family. TSP-1 and TSP-2 are potent antiangiogenic proteins. However, angiogenic properties of the 3 other TSPs, which do not contain the domains associated with the antiangiogeneic activity of TSP-1 and TSP-2, have not been explored. In our previous studies, we found that TSP-4 is expressed in the vascular matrix of blood vessels of various sizes and is especially abundant in capillaries. We sought to identify the function of TSP-4 in the regulation of angiogenesis. APPROACH AND RESULTS: The effect of TSP-4 in in vivo angiogenesis models and its effect on angiogenesis-related properties in cultured cells were assessed using Thbs4(-/-) mice, endothelial cells (EC) derived from these mice, and recombinant TSP-4. Angiogenesis was decreased in Thbs4(-/-) mice compared with wild-type mice. TSP-4 was detected in the lumen of the growing blood vessels. Mice expressing the P387 TSP-4 variant, which was previously associated with coronary artery disease and found to be more active in its cellular interactions, displayed greater angiogenesis compared with A387 form. Lung EC from Thbs4(-/-) mice exhibited decreased adhesion, migration, and proliferation capacities compared with EC from wild-type mice. Recombinant TSP-4 promoted proliferation and the migration of EC. Integrin α2 and gabapentin receptor α2δ-1 were identified as receptors involved in regulation of EC adhesion, migration, and proliferation by TSP-4. CONCLUSION: TSP-4, an extracellular matrix protein previously associated with tissue remodeling, is now demonstrated to possess proangiogenic activity.

Updated Review of Treatment of Androgenetic Alopecia.

Alopecia, a widespread issue affecting both genders, often manifests as androgenetic alopecia, although a thorough examination is needed to rule out other causes. This chapter focuses on the treatment of androgenetic alopecia. Finasteride and minoxidil, the Food and Drug Administration-approved treatments, offer stability and in some cases improvement in scalp coverage. Platelet-rich plasma exhibits positive results as an off-label alopecia therapy. For eligible individuals, hair transplantation proves effective, using healthy follicular units to restore hair-bearing areas. Multiple options allow for the tailoring of interventions to each patient.

Favorable Outcome Perception in Facial Selective Neurectomy.

OBJECTIVE: Facial selective neurectomy (SN) improves facial function by denervation of muscles antagonistic to the smile in nonflaccid facial paralysis (NFFP) patients. This study aims to assess whether and which objective facial function metrics affect favorable SN outcome in NFFP patients, as perceived by facial nerve (FN) practitioners. STUDY DESIGN: Retrospective cohort study. SETTING: NFFP patients who underwent SN at the facial nerve center. METHODS: Standardized preoperative and postoperative facial photographs of patients undergoing SN were analyzed using clinician-graded measures (eFACE) and automated facial measurement (Emotrics). Favorable outcome was ranked subjectively by 3 independent FN practitioners. Correlations between objective metrics and favorable subjective outcome were examined. RESULTS: Fifty-eight SN cases were included. Oral commissure excursion with smile, interlabial distance, and lower lip movement were all considered statistically significantly important for favorable outcome perception. Each +1 mm of smile excursion increases the odds of a favorable outcome by 75.4% (odds ratio [OR]: 1.754). Each +1 mm of interlabial distance asymmetry decreases the odds of a favorable outcome by 24.7% (OR: 0.753). Each +1-point change in lower lip movement eFACE score increases the odds of a favorable outcome by 2.7% (OR: 1.027). CONCLUSION: Several smile metrics contribute to favorable SN outcome perception among FN practitioners. Smile excursion, interlabial distance, and lower lip movement were significant predictors of success. These observations may be extrapolated to other facial reanimation interventions and serve surgeons and patients during counseling and expectation management, and during surgery.

Facial Nerve Exploration for Known or Suspected Transection: The Massachusetts Eye and Ear Experience.

Background: There is no ideal test to determine likelihood of spontaneous recovery after post-traumatic and postsurgical facial palsy (FP). Objective: Among patients with unexpected FP undergoing facial nerve (FN) exploration for suspected discontinuity, we endeavored to discern whether intraoperative findings, repair type, and time to exploration impact FN recovery, as measured by electronic Facial Clinimetric Evaluation (eFACE) and FaCE scales. Methods: Retrospective cohort study of 42 adult patients who underwent FN exploration. Results: FN injury resulted from either surgery (n = 29) or trauma (n = 13). Average time to repair was 68.4 (standard deviation 79.6) days. Postoperative improvements were observed in total eFACE (73.3-86.5; p < 0.0001) and FaCE (21.5-38.1; p = 0.0214) scores. Distal FN injuries were most common (n = 29) and had best recovery (percentage change in eFACE 57.2% vs. 34.3% main trunk, p = 0.0306). Discontinuity injuries (n = 33) repaired with primary coaptation (n = 18) had noninferior outcomes compared with cable graft repair (n = 16; percentage change in eFACE 49.6% vs. 39.2%, p = 0.3470). Denervation times <3 months yielded better recovery using percentage change in eFACE score (56.9% vs. 33.1%, p = 0.0270). Conclusions: Surgical exploration for unexpected FP allows for direct visualization of anatomical nerve status and timely repair.

Variation in the Price of Head and Neck Surgical Oncology Procedures.

Health care costs can present a significant strain on patients with head and neck cancer. It remains unclear how much prices may vary among hospitals providing care and what factors lead to differences in prices of surgical procedures. A cross-sectional analysis of private payer-negotiated prices was performed for 10 commonly performed head and neck surgical oncology procedures. In total, 896 hospitals disclosed prices for at least 1 common head and neck surgical oncology procedure. Wide variation in negotiated surgical prices was identified. Across-center ratios ranged from 6.2 (partial glossectomy without primary closure) to 22.8 (excision of tongue lesion without closure). For-profit hospital ownership structure and geographic region outside of the northeast United States were associated with increased prices. For example, private payer-negotiated prices for direct laryngoscopy with biopsy were on average $2083 greater at for-profit hospitals when compared with nonprofit hospitals ($5215 vs $3132, P < .001). Further research comparing prices and outcomes is needed.

Facial Filler in Facial Paralysis: A Prospective Case Study and Multidimensional Assessment.

Background: Facial filler is emerging as a nonsurgical alternative for addressing static asymmetry in facial paralysis (FP). Objectives: To elucidate the patient experience for facial filler and to facilitate preprocedure counseling and education. Materials and Methods: Patients receiving hyaluronic acid filler for FP at a tertiary academic medical center were prospectively recruited. Primary outcomes included patient-reported pain, facial symmetry (on a visual analog scale), and the results of quality-of-life surveys (FACE-Q satisfaction with facial appearance [SFA], FACE-Q psychosocial distress [PSD], Patient Health Questionnaire-9 [PHQ-9], and Euro Quality of Life 5-Dimension [EQ5D]) preprocedure and at 1 and 14 days postprocedure. Results: Twenty patients (90% women, average age 55 ± 11) completed the study. Sites of filler included the cheek, lower lip, nasolabial fold, chin, and temple regions. Patients reported minimal pain at postprocedure days (PPDs) 1 and 14. Patient-perceived symmetry scores improved significantly (p < 0.0001), as did FACE-Q SFA and FACE-Q PSD scores (p < 0.0001, <0.0001) when comparing preprocedure with PPD 14. Depression, assessed by PHQ-9, and the anxiety/depression domain of EQ5D, decreased after treatment (p = 0.016, 0.014) but no change was observed in the other domains of EQ5D. Conclusion: Facial filler for FP can be performed with minimal morbidity (pain, impact on daily routine, and complications) and leads to improvements across multiple psychosocial domains.

Hospital Prices for Pediatric Tympanostomy Tube Placement and Adenotonsillectomy in 2021.

OBJECTIVES: Hospital prices vary substantially for myringotomy with tympanostomy tube placement (M&T) and adenotonsillectomy (T&A). The Centers for Medicare and Medicaid Services recently implemented hospital price transparency requirements to help families make financially informed decisions about where to seek care. We sought to determine price availability and the extent of price variation for these procedures. METHODS: We performed a cross-sectional analysis of the Turquoise Health Hospital Rates Data Platform, which extracts prices for facility fees from publicly available hospital chargemasters. We determined the proportion of hospitals serving pediatric patients that published payer-specific prices for M&T and T&A. We additionally characterized the extent of variation in payer-specific prices both across and within hospitals. RESULTS: Approximately 40% (n = 909 of 2,266 hospitals) serving pediatric patients disclosed prices for M&T or T&A. Among disclosing hospitals, across-center ratios (adjusted for Medicare hospital wage indices) ranged from 11.0 (M&T; 10th percentile adjusted median price: $536.80 versus 90th percentile adjusted median price: $5,929.93) to 23.4 (revision adenoidectomy age >12 years; 10th percentile: $393.82 versus 90th percentile: $9,209.88). Median within-center price ratios for procedures ranged from 2.2 to 2.7, indicating that some private payers reimbursed the same hospital more than twice as much as other payers for the same procedure. CONCLUSION: The majority of hospitals serving pediatric patients were non-compliant with federal requirements to disclose prices for M&T and T&A. Among disclosing hospitals, there was wide variation in payer-specific prices between and within institutions. Further research is necessary to understand whether disclosure of prices will enable families to make more financially informed decisions. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:948-955, 2023.

Hospital-Negotiated Pricing of Cochlear Implants.

Access to cochlear implantation can be restricted by financial burden, and little is known about the extent to which cochlear implant (CI) devices prices may vary between hospitals or manufacturers. We performed a cross-sectional analysis of private payer-negotiated prices for CI devices. In total, 161 hospitals were analyzed. Prices varied widely across hospitals and between payers. Despite clinical equipoise between manufacturers with regards to CI user outcomes, significant differences in prices were identified, with higher prices for MED-EL ($38,478 ± 2633) than for Cochlear Ltd. ($34,150 ± 2418, p < .001). Markup analysis for Cochlear Ltd. devices revealed a mean 58.5% ± 7.4% markup in excess of the company's average sales price ($24,649). Negotiated prices were also at least $5000 lower when all 3 brands were offered at the same center (p < .05). Further research examining the influence of patient outcomes and hospital volume on prices are needed.

Variations in Payer-Negotiated Prices for Head and Neck Reconstructive Surgery.

OBJECTIVE: Little is known about pricing for reconstructive procedures of the head and neck. As of January 2021, the Centers for Medicare and Medicaid Services requires hospitals to disclose payer-negotiated prices for services, offering new insight into prices for privately insured patients. STUDY DESIGN: Cross-sectional analysis. SETTING: Turquoise database. METHODS: Payer-negotiated facility fees for 41 reconstructive surgeries were grouped by procedure type: primary closure, skin grafts, tissue rearrangement, locoregional flaps, or free flaps. Prices were normalized to account for local labor costs, then calculated as percent markup in excess of Medicare reimbursement. The mean percent markup between procedure groups was compared by the Kruskal-Wallis test. Subset analyses were performed to compare mean percent markup using a Student's t test. We also assessed price variation by calculating the ratio of 90th/10th percentile mean prices both across and within hospitals. RESULTS: In total, 1324 hospitals (85% urban, 81% nonprofit, 49% teaching) were included. Median payer-negotiated fees showed an increasing trend with more complex procedures, ranging from $379.54 (interquartile range [IQR], $230.87-$656.96) for Current Procedural Terminology (CPT) code 12001 ("simple repair of superficial wounds ≤2.5 cm") to $5422.60 ($3983.55-$8169.41) for CPT code 20969 ("free osteocutaneous flap with microvascular anastomosis"). Median percent markup was highest for primary closure procedures (576.17% [IQR, 326.28%-1089.34%]) and lowest for free flaps (99.56% [37.86%-194.02%]). Higher mean percent markups were observed for rural, for-profit, non-Northeast, nonteaching, and smaller hospitals. CONCLUSION: Wide variation in private payer-negotiated facility fees exists for head/neck reconstruction surgeries. Further research is necessary to better understand how pricing variation may correlate with out-of-pocket costs and quality of care.